Identification of DNA methylation-independent epigenetic events underlying clear cell renal cell carcinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Gangning Liang
PROVIDER: E-GEOD-70303 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Genome-wide analysis of endogenous and exogenous methylation in human ccRCC tumor and adjacent normal tissue to determine DNA methylation and chromatin structure states in ccRCC.
2016-03-15 | GSE70303 | GEO
Project description:Alterations in chromatin accessibility independent of DNA methylation can affect cancer-related gene expression, but are often overlooked in conventional epigenomic profiling approaches. In this study, we describe a cost-effective and computationally simple assay called AcceSssIble to simultaneously interrogate DNA methylation and chromatin accessibility alterations in primary human clear cell renal cell carcinomas (ccRCC). Our study revealed significant perturbations to the ccRCC epigenome, and identified gene expression changes that were specifically attributed to the chromatin accessibility status whether or not DNA methylation was involved. Compared to commonly mutated genes in ccRCC, such as the von Hippel-Lindau (VHL) tumor suppressor, the genes identified by AcceSssIble comprised distinct pathways and more frequently underwent epigenetic changes, suggesting that genetic and epigenetic alterations could be independent events in ccRCC. Specifically, we found unique DNA methylation-independent promoter accessibility alterations in pathways mimicking VHL deficiency. Overall, this study provides a novel approach for identifying new epigenetic-based therapeutic targets, previously undetectable by DNA methylation studies alone, that may complement current genetic-based treatment strategies. Examination of 3 different histone modifications in 2 patient tumor and adjacent normal samples.
2016-03-15 | E-GEOD-75597 | biostudies-arrayexpress
Project description:Alterations in chromatin accessibility independent of DNA methylation can affect cancer-related gene expression, but are often overlooked in conventional epigenomic profiling approaches. In this study, we describe a cost-effective and computationally simple assay called AcceSssIble to simultaneously interrogate DNA methylation and chromatin accessibility alterations in primary human clear cell renal cell carcinomas (ccRCC). Our study revealed significant perturbations to the ccRCC epigenome, and identified gene expression changes that were specifically attributed to the chromatin accessibility status whether or not DNA methylation was involved. Compared to commonly mutated genes in ccRCC, such as the von Hippel-Lindau (VHL) tumor suppressor, the genes identified by AcceSssIble comprised distinct pathways and more frequently underwent epigenetic changes, suggesting that genetic and epigenetic alterations could be independent events in ccRCC. Specifically, we found unique DNA methylation-independent promoter accessibility alterations in pathways mimicking VHL deficiency. Overall, this study provides a novel approach for identifying new epigenetic-based therapeutic targets, previously undetectable by DNA methylation studies alone, that may complement current genetic-based treatment strategies.
2016-03-15 | GSE75597 | GEO
Project description:Genome wide DNA methylation profiling of clear cell renal cell carcinoma (ccRCC) tissue versus matched normal kidney tissue. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in tumor and adjacent normal kidney tissue samples from ccRCC patients. Samples included 46 paired fresh frozen ccRCC tumor and adjacent normal kidney tissues. Bisulphite converted DNA from the 92 samples were hybridised to the Illumina Infinium 450 Human Methylation Beadchip v1.2
2015-10-26 | E-GEOD-61441 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are short single stranded RNAs that are associated with gene regulation at the transcriptional and translational level. Changes in their expression were found in a variety of human cancers. Because of the lack of corresponding data in clear renal cell carcinoma (ccRCC) we have performed genome-wide expression profiling of miRNAs using microarray analysis and quantification of specific miRNAs by TaqMan real-time RT-PCR. Matched malignant and non-malignant tissue samples from two independent 12 ccRCC sets were profiled. The microassay-based experiments identified 14 overexpressed and 20 downregultaed miRNAs in malignant samples. Expression in ccRCC tissue samples compared to matched non-malignant samples measured by RT-PCR was increased by 2.7 to 28fold for the hsa-mir-16, -452, -224, -155, and -210, but decreased by 6.2 to 96fold for hsa-mir-200b, -363, , -429, -200c, -514, and -141. No significant associations between these differentially expressed miRNAs and the clinico-pathological factors tumor stage, grade, and survival rate were found. Nevertheless, malignant and non-malignant tissue could clearly be differentiated by their miRNA profile . A combination of miR-141 and miR-155 resulted in a 96% overall correct classification of samples. The presented differential miRNA pattern provides a solid basis for further validation including functional studies. The study was performed with two independent sample sets. For each set 12 kidney tissue sample pairs were derived from adult patients undergoing radical nephrectomy at the University Hospital Charité. All tumor types were clear renal cell carcinoma. Tumor classification and stage were established according to the 2002 TNM System and the 2004 WHO Classification. Matched malignant (#NC (e.g. 2NC)) and non-malignant (#NN (e.g. 1NN)) tissue samples from two independent 12 ccRCC sets were profiled.
2010-06-25 | E-GEOD-12105 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of clear cell renal cell carcinoma (ccRCC) tissue versus matched normal kidney tissue. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in tumor and adjacent normal kidney tissue samples from ccRCC patients. Samples included 46 paired fresh frozen ccRCC tumor and adjacent normal kidney tissues.
2015-10-26 | GSE61441 | GEO
Project description:We aimed to assess differences in miRNA expression profiles in transcriptomic molecular subtypes of ccRCC (Beuselinck et al, Clinical Cancer Research 2015) and to correlate miRNAs with overal survival since diagnosis of ccRCC. Sequencing was done for 129 primary ccRCC (formalin-fixed paraffin-embedded surgical resection specimens, previously untreated) and 16 normal kidney specimens. Normal kidney was obtained from the nephrectomy specimens at time of ccRCC removal, in tissue blocks containing only normal kidney (so nót the normal kidney immediately adjacent to ccRCC). The samples were sequenced in 2 major batches (2014 and 2017).
2020-07-22 | E-MTAB-9380 | biostudies-arrayexpress
Project description:The understanding of metastatic spread is limited and molecular mechanisms causing particular characteristics of metastasis are largely unknown. This comprises the extremely varying dormancy periods of tumor cells in the secondary organ after metastatic spread, represented by the disease-free survival (DFS) of the patients, or differing numbers of metastases in different patients. Knowing the molecular fundamentals of these phenomena would support the individual prediction of patients´ outcome and facilitate the decision for an appropriate monitoring and therapy regime. In a first study (PMID 19391132) we analyzed the transcriptome-wide expression profiles of 20 pulmonary metastases of renal cell carcinoma (Met1-9, Met11-18, Met20, Met23, Met25) to identify expression patterns associated with the dormancy period and the number of metastases per patient. Pre-processed and analyzed data for this study are available in GEO Series GSE14378. In this second study, we validated the DFS-associated expression pattern from the first study on four further metastases and also included primary ccRCC with different DFS. For this, the microarray data of all metastases and primary tumors were pre-processed together. The aim of this second study was to identify those genes, which are differentially expressed in metastases developed after different dormancy periods and which are already deregulated in primary tumors. Genes differentially expressed in synchronously vs. metachronously metastases might contribute functionally to the dormancy period. Genes already deregulated in primary ccRCC might be suitable for prognostic purposes. metastases manifested synchronously or metachronously (DFS less than or equal to 9 months compared with DFS greater than or equal to 60 months); primary ccRCC which developed synchronous or metachronous metastases (DFS less than or equal to 6 months compared with DFS greater than or equal to 45 months)
2010-07-30 | E-GEOD-22541 | biostudies-arrayexpress
Project description:Patients undergoing either partial or radical nephrectomy at William Beaumont Hospital (Royal Oak, MI) were consented prior to surgery with local IRB oversight. Samples were collected at time of surgery and stored at -80°C according to CAP (College of American Pathologist)-accredited standard operating procedures. Disease pathology of frozen samples was validated with hematoxylin and eosin stained tissue sections from adjacently collected formalin fixed paraffin embedded tissue. The objective of this study was to examine the gene expression patterns of clear cell carcinoma in relation to adjacent normal kidney as well as other benign kidney conditions. In particular, the goal was to identify gene expression that could differentiate high grade ccRCC from low grade ccRCC. Samples from patients with high grade ccRCC (Fuhrman grades 3 & 4, n=16) were compared to normal kidney samples (n=14) and also to samples from patients with benign kidney conditions (n=6). Samples from patients with low grade ccRCC (Fuhrman grades 1 & 2, n=13) were then also compared to normal kidney samples (n=14) and also to samples from patients with benign kidney conditions (n=6).
2016-01-04 | E-GEOD-68417 | biostudies-arrayexpress
Project description:Clear cell renal cell carcinoma (ccRCC) is the most common adult renal cancer. Although the molecular characteristics of ccRCC are currently being studied, the biologically and clinically relevant ccRCC methylome remains to be elucidated. To explore the RCC hypermethylome we employed massive sequencing of methyl-binding protein enriched DNA and validated the biological relevance of the identified hypermethylated sites by pharmacological inhibition of DNA methylation. We identified four candidate tumor suppressor genes (GREM1, LAD1, NEFH, and NEURL) of which promoter CpG island hypermethylation was strongly predictive for ccRCC survival in two independent series (n=150 and n=185) of ccRCC primary samples. The four markers combined are strongly associated with risk for cancer-related death in the test series (HR 3.64, 95% CI 1.02-13.01) as well as, independently of other clinicopathological characteristics, in the validation series (HR 7.54, 95% CI 2.68-21.19) using Cox proportional hazard models. According to Harrell’s C statistics and the Akaike Information Criterion (AIC) the four marker panel provides the best predictive capacity with the best fit of the model as assessed for the tested markers. These results provide novel insights into the ccRCC hypermethylome and identify a strong methylation marker panel to potentially guide personalized ccRCC patient management. Preliminary to implementation of this marker panel into clinical practice, enrollment of these patients in a Phase-III trial to study adjuvant treatment efficacy is essential. 4 independant clear cell renal cancer cell lines were used before and after treatment with the DNA methylation inhibitor AZA or the HAZA inhibitor TSA.
2013-11-22 | E-GEOD-33916 | biostudies-arrayexpress